Download Antibiotic Resistance

Antibiotic Resistance
Background information, current issues and policy,
and the veterinarian’s role
Outline
• Recent news and importance of issue
• Antibiotics: information, mode of action
• Factors that contribute to resistance
– In the free environment
– In animals
• Resistance: a working definition
• The Veterinarians role and current policy
• Discussion
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Meropenem, an
example of a
carbapenem
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www.usatoday.com
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Level of Importance
• One of the most important
issues for current treatment
for human and animal
patients
• Will probably become the
most challenging treatment
complication while we are
practicing
• 68% of acute respiratory
tract visits were prescribed
antibiotics.
• Of these, 80% of the
prescriptions were
unnecessary according to
CDC guidelines1.
1) Scott JG, Cohen D, DiCicco-Bloom B, Orzano AJ, et al: Antibiotic use in acute
respiratory infections and the ways patients pressure physicians for a
prescription. J Fam Pract: 50(10): 853-8, 2001.
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Antibiotics
• Take advantage of a difference between bacterial cells and
host cells to be selectively bactericidal or bacteriostatic
• FDA has four approved uses of antibiotics: treatment,
prevention, control, and growth promotion/feed efficiency
Gram-positive cell wall
Pictures from Doug Johnson
Gram-negative cell wall
Eukaryotic cell membrane
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http://en.wikipedia.org/wiki/File:Antibiotics_action.png
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Transpeptidation inhibition
• Transpeptidation is the cross-linking of peptides within cell
wall. Necessary for cell wall integrity
• Penicillin-binding proteins (pbp) catalyze this process
• Penicillin and related antibiotics (β-lactams) inhibit this
process
+
Transpeptidation
by pbp
Penicillin
Cell lysis and death
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MRSA
• Methicillin
Resistant
Staphylococcus
aureus
Multiple Resistant
Staphylococcus
aureus?
• Skin infections are common and relatively easy to treat
• Infections acquired in healthcare settings, both human and
animal, are often more severe
–
–
–
–
Immunocompromised or vulnerable to infection
Post-operative risk
Presence of many ill individuals
Large reservoir for infection
cdc.gov
• Most human hospitals have protocols in place for Multiple
Drug Resistant Organisms
• Animal hospitals are lacking in robust protocols
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Tracking Resistance
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Tracking Resistance
HealthMap.org
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Resistance – A Working Definition
• Antibiotic resistance is the ability of bacteria to resist the
effects of an antibiotic. In a clinical setting this means the
persistence of disease.
• Antibiotic resistance occurs when bacteria change in some
way that reduces or eliminates the effectiveness of drugs,
chemicals, or other agents designed to cure or prevent
infections.
• Huge selective pressure is placed on bacteria when antibiotics
are present
cdc.gov
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Resistance – possible causes
• Mutation – change of drug target
– Inevitable mutations that occur normally are
enhanced by increased rates of DNA damage
• Conjugation – direct transfer of genes
• Transformation – eDNA is incorporated
into cell
• Transduction – transfer of genes via
viruses
• Destruction or inactivation of drug
• Ability to pump drug out
http://kentsimmons.uwinnipeg.ca/16cm05/1116
/16monera.htm
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Determining Resistance
Disk Diffusion Assay
Aminoglycoside
Quinolone
Tetracycline
Ciprofloxacin
NARMS Retail Meat Annual Report, 2007
Cephamycin
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Contributing factors to resistance- Biofilms
• The extreme majority of microbes do
not live as isolated, pure cultures in the
planktonic state
• Rather they exist in complex
communities surrounded by the
extracellular polymeric substance (EPS)
• The EPS consists of
–
–
–
–
Protein
eDNA
Sugars
Water
Confocal Scanning Laser Microscopy
Flemming and Wingender. Nature reviews 2010
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Contributing factors to resistance- Biofilms
• Biofilms offer many advantages over planktonic cells:
– Protective barrier from direct harm and predation
– Complex array of enzymes that otherwise may not be available to a
particular species
– Retention and storage of water and nutrients
– Maintenance of chemical gradients
– A diverse set of nuclear material for exchange (horizontal transfer)
Flemming and Wingender. Nature reviews 2010
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Contributing factors to resistance- Biofilms
• Implications for human and
animal health
• Also consider achieving and
maintaining the minimum
inhibitory concentration in
tissues (different tissue
types having the same effect
as a biofilm)
Photo from Doug Johnson
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Contributing factors to resistance- Exposure
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Kaufmann et al. 2010
Contributing factors to resistance- Exposure
LexA
inhibition
• Causes for continued low level exposure:
–
–
–
–
Non-therapeutic dose
Missed dose/early discontinuation
Did not achieve MIC at site of infection
Not the appropriate antibiotic
Kaufmann et al. 2010
Cirz et al. (2005)
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Briefing on Current Issue
• July 3, 2008. FDA issued an order that prohibited the
extralabel use of cephalosporin drugs in food-producing
animals
• The AVMA recommended the FDA postponed the ruling until
a risk assessment was preformed
– Felt there was a lack of scientific evidence
– No promise that it would benefit human health
– Unintended consequences of animal health, food safety
• In November of 2008 the FDA withdrew the order
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Briefing on Current Issue
• The Preservation of Antibiotics for Medical Treatment Act of
2009 - PAMTA (S.619/H.R.1549)
• Eliminate the use of non-therapeutic use of antibiotics that
are important in human health, meant to decrease the
development of antibiotic resistant bacteria
– Non-therapeutic use = use of a drug as a feed or water additive for an
animal in the absence of any clinical sign of disease
– Drugs listed: penicillin, tetracycline, macrolide, sulfonamide, or any
drug that is used in humans to treat and prevent disease
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The AVMA Position on PAMTA
• The AVMA opposes this legislation
–
–
–
–
Increase in animal disease and death
Compromise disease prevention and control
PAMTA is not risk-based (backed up by a solid risk assessment)
Contrary to the practice of veterinary medicine
• Current layers of protection
• Conflicting scientific data on risk to humans
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What YOU can do
• Need for more information on to what extent antibiotics in
animals play a role in human health
• Novel drugs are desperately needed
• Properly set up protocols should be established and followed
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What do you think?
• Now everyone has plenty of basic information and a general
knowledge of the importance of the issue.
• What do you think about …?
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–
–
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PAMTA and the current AVMA position
Current veterinary practices (draw from your own experiences)
Current human medicine practices (draw from your own experiences)
How things will change in the next 10 years (from now to time when
some of you may be practicing)
– Any general thoughts?
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